Clinical Manifestations of Purine Metabolism Disorders

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Questions and Answers

What is a potential treatment option for defects in the purine salvage pathway?

Monoclonal antibody therapy

Intravenous immunoglobulin

Haploidentical bone marrow transplantation (correct)

CD34+ cell therapy

Which enzyme replacement therapy is applicable for adenosine deaminase deficiency?

Phenylalanine hydroxylase

Lipoprotein lipase

ADA enzyme replacement therapy (correct)

Hyaluronic acid

Which of the following is a key clinical manifestation in a patient with adenosine deaminase deficiency?

Hypertension

Lethargy (correct)

Persistent headaches

Severe acne

Which of the following purines is comprised of a nitrogenous base?

Adenine Signup and view all the answers

What clinical symptom may suggest immunodeficiency in a child?

Frequent upper respiratory infections Signup and view all the answers

What is a characteristic physical examination finding in a 6-month-old with adenosine deaminase deficiency?

Hypotonia Signup and view all the answers

Which diagnosis might be considered in a child presenting with decreased sensorium and hepatosplenomegaly?

Adenosine deaminase deficiency Signup and view all the answers

In the context of adenosine deaminase deficiency, what is the primary metabolic consequence of the condition?

Accumulation of toxic metabolites Signup and view all the answers

What is the primary cause of gout in patients with Lesch-Nyhan syndrome?

Inadequate production of purine nucleotides Signup and view all the answers

Which joint is most commonly affected in patients with gout?

Metatarsophalangeal Signup and view all the answers

How does hyperuricemia contribute to urate crystal formation?

By decreasing the solubility of uric acid Signup and view all the answers

What is the inheritance pattern of Lesch-Nyhan syndrome?

X-linked recessive Signup and view all the answers

What primary symptom progresses from mono-arthritis to polyarthritis in gout?

Joint swelling and pain Signup and view all the answers

What metabolic deficiency is linked to Lesch-Nyhan syndrome?

HGPRT deficiency Signup and view all the answers

Which aspect of temperature is relevant in urate crystal formation in extremities?

Decreased local temperature Signup and view all the answers

Which of the following conditions can contribute to hyperuricemia?

Inadequate dietary management Signup and view all the answers

What is the role of 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase in inflammation?

It promotes the production of PRPP, leading to increased uric acid. Signup and view all the answers

Which condition is characterized by the crystallization of uric acid in the joints?

Gout Signup and view all the answers

What is the primary consequence of increased purine nucleotide degradation?

Formation of sodium urate crystals. Signup and view all the answers

What clinical condition is associated with elevated uric acid levels?

Gout Signup and view all the answers

Which syndrome is linked to defects in the purine salvage pathway?

Lesch-Nyhan Syndrome Signup and view all the answers

What is a common symptom associated with the presence of urate crystals in the joints?

Extreme swelling and tenderness Signup and view all the answers

How does inflammation affect pH levels in the affected area?

Inflammation decreases pH promoting lactic acid production. Signup and view all the answers

What is the impact of hyperuricemia on joint health?

Results in the formation of sodium urate crystals. Signup and view all the answers

What is a primary mechanism of action for colchicine in treating gout?

Inhibit microtubule formation Signup and view all the answers

Which condition would likely lead to the use of uricosuric agents like probenecid?

Underexcretion of uric acid Signup and view all the answers

What typical side effect is associated with colchicine?

Nitropenia Signup and view all the answers

What is the normal serum uric acid level indicated for gout diagnosis?

5-6 mg/dL Signup and view all the answers

What diagnostic finding is associated with gout during arthrocentesis?

Negative birefringent crystals Signup and view all the answers

What is a likely consequence of urate crystals rupturing phagocytes in gout?

Increased joint swelling and pain Signup and view all the answers

In the purine catabolic pathway, what enzyme's activity is inhibited by allopurinol?

Xanthine oxidase Signup and view all the answers

Which of the following is not true regarding colchicine?

It is used during acute attacks Signup and view all the answers

What is the primary reason why uric acid can crystallize in the blood?

It is poorly soluble and the saturation level is exceeded. Signup and view all the answers

What role does the salvage pathway play in purine metabolism?

It prevents the degradation of purines into uric acid. Signup and view all the answers

How does allopurinol function in treating gouty arthritis?

By inhibiting the production of uric acid from purines. Signup and view all the answers

What is the primary metabolic issue associated with gouty arthritis?

Excessive conversion of hypoxanthine to uric acid. Signup and view all the answers

What physiological state can lead to the crystallization of uric acid?

Saturation of uric acid in the blood. Signup and view all the answers

What is the chemical form of uric acid present in blood under physiological conditions?

It exists in an ionized form. Signup and view all the answers

What is the most likely trigger for the acute attack of gout in the presented case?

Excessive alcohol consumption. Signup and view all the answers

What is the role of colchicine in managing gout symptoms?

It reduces inflammation caused by uric acid crystals. Signup and view all the answers

Study Notes

Overproduction and Clinical Manifestations

De novo synthesis of purines is a critical metabolic pathway involved in nucleotide production.
Defects in the purine salvage pathway can lead to various disorders, including adenosine deaminase (ADA) deficiency and Lesch-Nyhan syndrome.
Inflammation from uric acid crystal deposition leads to conditions like gout.
Clinical presentations include immunocompromised states reflected by decreased sensorium, hepatosplenomegaly, lethargy, and joint pain.

Case Studies

Case No. 1: Adenosine Deaminase Deficiency
- Presents in a 6-month-old with lethargy, low appetite, and unresponsive diaper rash.
- Symptoms of frequent upper respiratory tract infections and hypotonia noted.
Case No. 2: Gouty Arthritis
- 43-year-old male experienced sudden, severe right big toe pain after excessive drinking.
- Gout results from high uric acid levels leading to sodium urate crystal formation in joints, causing swelling and tenderness.

Purine Metabolism

Impairments in purine metabolism result in hyperuricemia and gout, with uric acid being toxic at high levels.
Uric acid is poorly soluble, leading to crystallization when blood saturation exceeds normal levels.
Disturbances in purine nucleotide production directly link to increased uric acid output.

Treatment Options

Potential treatments include haploidentical bone marrow transplantation, ADA enzyme replacement therapy, and ADA gene therapy for ADA deficiency.
For gout management, medications like allopurinol (xanthine oxidase inhibitor) and colchicine (inhibits microtubule formation) are used.
Uricosuric agents, such as probenecid, enhance uric acid excretion in patients with underexcretion.

Clinical Correlations

Lesch-Nyhan syndrome is a genetic condition associated with mental retardation and self-destructive behavior; related to reduced purine salvage.
Gouty arthritis primarily affects the metatarsophalangeal joint; rapid onset of symptoms can indicate a gout flare.
Diagnosis of gout relies on the detection of negatively birefringent urate crystals in synovial fluid.

Diagnostic Tests

Elevated serum uric acid levels signal potential gout; however, levels may normalize during acute attacks.
Urinary uric acid excretion over 800 mg per 24 hours is indicative of conditions related to uric acid metabolism.
Arthrocentesis can reveal characteristic crystal formations aiding in gout diagnosis.

Summary of Mechanisms

Microtubule inhibition by colchicine reduces inflammatory responses in joints.
Increased activity of 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase promotes purine synthesis, exacerbating conditions related to uric acid excess.
Uric acid crystals preferentially form in cooler extremities, contributing to gout pathophysiology.

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Description

This quiz explores the clinical implications of purine metabolism disorders, including adenosine deaminase deficiency and gout. Case studies highlight symptoms and presentations, illustrating the impact of purine overproduction on health. Test your knowledge on these critical metabolic pathways and their disorders.